Comparative Behavioral Correlation of High and Low-Performing Mice in the Forced Swim Test.

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy.

Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat Primary Astrocytes.

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation.

Effects of Several Cosmetic Preservatives on ROS-Dependent Apoptosis of Rat Neural Progenitor Cells.

Benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea are commonly used preservatives in cosmetics. Recent reports suggested that these compounds may have cellular and systemic toxicity in high concentration. In addition, diazolidinyl urea and imidazolidinyl urea are known formaldehyde (FA) releasers, raising concerns for these cosmetic preservatives.

Activation of Glucagon-Like Peptide-1 Receptor Promotes Neuroprotection in Experimental Autoimmune Encephalomyelitis by Reducing Neuroinflammatory Responses.

The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis. Both components of the signaling axis, GLP-1 and GLP-1R proteins, are expressed in neurons, astrocytes, and microglia in the spinal cord of normal mice.

Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation.

Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia.

Supplementation of Korean Red Ginseng improves behavior deviations in animal models of autism.

Background: Autism spectrum disorder (ASD) is heterogeneous neurodevelopmental disorders that primarily display social and communication impairments and restricted/repetitive behaviors. ASD prevalence has increased in recent years, yet very limited therapeutic targets and treatments are available to counteract the incapacitating disorder. Korean Red Ginseng (KRG) is a popular herbal plant in South Korea known for its wide range of therapeutic effects and nutritional benefits and has recently been gaining great scientific attention, particularly for its positive effects in the central nervous system.

Ginkgo biloba Extract (EGb 761®) Inhibits Glutamate-induced Up-regulation of Tissue Plasminogen Activator Through Inhibition of c-Fos Translocation in Rat Primary Cortical Neurons.

EGb 761(®) , a standardized extract of Ginkgo biloba leaves, has antioxidant and antiinflammatory properties in experimental models of neurodegenerative disorders such as stroke and Alzheimer's disease. Tissue plasminogen activator (tPA) acts a neuromodulator and plays a crucial role in the manifestation of neurotoxicity leading to exaggerated neuronal cell death in neurological insult conditions. In this study, we investigated the effects of EGb 761 on the basal and glutamate-induced activity and expression of tPA in rat primary cortical neurons.

High sucrose consumption during pregnancy induced ADHD-like behavioral phenotypes in mice offspring.

In recent years, the average consumption of sugar in humans from all ages has remarkably increased, exceeding the recommended limit. Pregnancy is a critical time for the global development of offsprings who are vulnerable to the deleterious effects of environmental factors. In this study, we investigated whether high sucrose consumption during pregnancy could affect the attention-deficit hyperactivity disorder (ADHD)-like neurobehavioral outcomes in offspring mice.

Proteinase 3 Induces Neuronal Cell Death Through Microglial Activation.

Proteinase 3 (PR3) is released from neutrophil granules and is involved in the inflammatory process. PR3 is implicated in antimicrobial defense and cell death, but the exact role of PR3 in the brain is less defined. Microglia is the major immune effector cells in the CNS and is activated by brain injury.

The Epigenetic Reader BRD2 as a Specific Modulator of PAI-1 Expression in Lipopolysaccharide-Stimulated Mouse Primary Astrocytes.

The post translational modification of lysine acetylation is a key mechanism that regulates chromatin structure. Epigenetic readers, such as the BET domains, are responsible for reading histone lysine acetylation which is a hallmark of open chromatin structure, further providing a scaffold that can be accessed by RNA polymerases as well as transcription factors. Recently, several reports have assessed and highlighted the roles of epigenetic readers in various cellular contexts.

Ginkgo biloba extract (Egb761) attenuates zinc-induced tau phosphorylation at Ser262 by regulating GSK3β activity in rat primary cortical neurons.

In the brain, an excessive amount of zinc promotes the deposition of β-amyloid proteins and the intraneuronal accumulation of neurofibrillary tangles composed of hyperphosphorylated tau proteins. These consequences are key neuropathological traits that reflect Alzheimer's disease. Egb761, a standardized Ginkgo biloba extract, is a powerful antioxidant known to exhibit neuroprotective actions.

Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia.

Vascular dementia (VaD) is the second most common form of dementia caused by cerebrovascular disease. Several recent reports demonstrated that cholinergic deficits are implicated in the pathogenesis of VaD and that cholinergic therapies have shown improvement of cognitive function in patients with VaD. However, the precise mechanisms by which donepezil achieves its effects on VaD are not fully understood.

Resveratrol down-regulates a glutamate-induced tissue plasminogen activator via Erk and AMPK/mTOR pathways in rat primary cortical neurons.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RSV) is a polyphenolic compound present in a variety of plant species (including grapes) that produces a myriad of biological activities including anti-inflammatory, antioxidant and neuroprotective effects. In this study, we investigate the effects of resveratrol on the basal and glutamate-stimulated expression and activity of a tissue plasminogen activator (tPA) that plays neuromodulatory or neurotoxic roles in many different neurological situations. Under basal conditions, resveratrol decreased the tPA expression and activity without affecting the tPA mRNA level in rat primary cortical neurons.

Valproic Acid Regulates α-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes.

Although the role of α-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of α-synuclein are unclear yet. We recently reported that α-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing α-synuclein in neuron, on α-synuclein expression in rat primary astrocytes.

Transcriptional Upregulation of Plasminogen Activator Inhibitor-1 in Rat Primary Astrocytes by a Proteasomal Inhibitor MG132.

Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1.

Proteinase 3 induces oxidative stress-mediated neuronal death in rat primary cortical neuron.

The recruitment of neutrophils into the cerebral microcirculation occurs, especially, in acute brain diseases like a focal cerebral ischemia and plays important role in pathological processes. Proteinase 3 is one of the three major proteinases expressed in neutrophils but no reports are available whether proteinase 3 can modulate neuronal survival. In this study, treatment of cultured rat primary cortical neuron with proteinase 3 induced overt reactive oxygen species production and decreased total glutathione contents as well as disruption of mitochondrial transmembrane potential.

Glucose deprivation reversibly down-regulates tissue plasminogen activator via proteasomal degradation in rat primary astrocytes.

Aims: Tissue plasminogen activator (tPA) is an essential neuromodulator whose involvement in multiple functions such as synaptic plasticity, cytokine-like immune function and regulation of cell survival mandates rapid and tight tPA regulation in the brain. We investigated the possibility that a transient metabolic challenge induced by glucose deprivation may affect tPA activity in rat primary astrocytes, the main cell type responsible for metabolic regulation in the CNS.

Main Methods: Rat primary astrocytes were incubated in serum-free DMEM without glucose.

Valproic acid induces astrocyte-dependent neurite outgrowth from cultured rat primary cortical neuron via modulation of tPA/PAI-1 activity.

Tissue plasminogen activator (tPA) is expressed in several regions of brain and plays regulatory roles such as neurite outgrowth, synaptic plasticity and long term potentiation. The activity of tPA is regulated by an endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1), which is expressed mainly in astrocytes. Valproic acid (VPA), a histone deacetylase inhibitor that is used for the treatment of epilepsy and bipolar disorders, promotes neurite extension, neuronal growth and has neuroprotective effect in neurodegenerative diseases.

Neuroprotective effects of valproic acid against hemin toxicity: possible involvement of the down-regulation of heme oxygenase-1 by regulating ubiquitin-proteasomal pathway.

During hemorrhagic stroke induced by intracerebral hemorrhage (ICH), brain injury occurs from the deleterious actions of hemoglobin byproducts; induction of heme oxygenase-1 (HO-1) also plays a critical role in the neurotoxicity in ICH. Valproic acid (VPA), which is a commonly used drug in the treatment of epilepsy, has been reported to have neuroprotective effects against various neuronal insults including ischemic stroke. We investigated the effect of VPA on HO-1-mediated neurotoxicity in an experimental model of ICH.

Regulation of tissue plasminogen activator/plasminogen activator inhibitor-1 by hydrocortisone in rat primary astrocytes.

Although originally known as a plasma serine protease involved in clot dissolution, tPA and its primary inhibitor, PAI-1, play crucial roles in synaptic reorganization and plasticity in the central nervous system. In contrast to the wide array of work conducted in neural cells, relatively little is known about the regulatory mechanism governing tPA/PAI-1 expression in astrocytes. Glucocorticoids (GCs) such as hydrocortisone regulate the expression of tPA/PAI-1 in various biological systems in a tissue-specific manner.

Biphasic regulation of tissue plasminogen activator activity in ischemic rat brain and in cultured neural cells: essential role of astrocyte-derived plasminogen activator inhibitor-1.

In brain, the serine protease tissue plasminogen activator (tPA) and its endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1) have been implicated in the regulation of various neurophysiological and pathological responses. In this study, we investigated the differential role of neurons and astrocytes in the regulation of tPA/PAI-1 activity in ischemic brain. The activity of tPA peaked transiently and then decreased in cortex and striatum along with delayed induction of PAI-1 in the inflammatory stage after MCAO/reperfusion injury.

The effects of IL-32 on the inflammatory activation of cultured rat primary astrocytes.

A new family of cytokine IL-32 has been implicated in pro-inflammatory immune responses several human diseases such as rheumatoid arthritis, inflammatory bowel diseases and vasculitis. In this study, we investigated the role of IL-32 in the inflammatory activation of cultured rat primary astrocytes. Treatment of IL-32 increased ROS production and augmented lipopolysaccharide-induced increased production of nitric oxide as well as the expression of iNOS.